Case 21 Discussion
Learning Objectives
- Review unique features of VEO-IBD
- Review the underlying drivers of disease
- Review the individualized evaluation for patients with VEO-IBD
EPAs
- EPA 1: Classify IBD phenotype, disease activity, and extraintestinal manifestations
- EPA 2: Use advanced diagnostic and therapeutic endoscopic and radiographic techniques in the management of IBD
- EPA 7: Manage IBD in special populations
- Very early onset inflammatory bowel disease (VEO-IBD) is defined as IBD that presents in infants and children less than 6 years of age.
- Patients presenting less than 2 years of age are further sub-categorized as having infantile-onset IBD and those presenting at less than 27 days of age can be classified as neonatal-onset IBD.
- VEO-IBD is increasing in incidence. VEO IBD features: more often involves colon and often severe course with poor response to conventional immunosuppressives. Due to increasing incidence it is important to be familiar with additional considerations when evaluating these patients.
- 15-20% have a monogenic defect (one gene is involved in causing the IBD phenotype). This contrasts with older patients who are more likely to have polygenic inheritance defects (multiple genes are involved in the IBD phenotype. Many of the monogenic defects that have been identified in patients with VEO-IBD are also found in primary immune deficiency syndromes which often present with GI symptoms. These defects can affect the following processes: IL-10 signaling defects, immune dysregulation, T and B cell dysfunction, phagocytic defects, hyperinflammatory and autoinflammatory dysfunction, and epithelial barrier dysfunction.
- Identification of VEO-IBD disorders with genetic testing (either whole exome or targeted gene panel) helps determine specific medical therapies and/or stem cell transplantation for disorders like CTLA4B deficiency, LRBA defects, IL-10 deficiency, XIAP, STXBP2, and FOXP3 deficiency.
- The goals of a diagnostic evaluation for VEO-IBD is to identify patients with an underlying genetic cause of their VEO-IBD, with an underlying primary immune deficiency, and/or those who could benefit from non-standard IBD therapies
References
- Kelsen, Judith R.∗; Sullivan, Kathleen E.†; Rabizadeh, Shervin‡; Singh, Namita; Snapper, Scott||,¶; Elkadri, Abdul#; Grossman, Andrew B.∗North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper on the Evaluation and Management for Patients With Very Early-onset Inflammatory Bowel Disease, Journal of Pediatric Gastroenterology and Nutrition: March 2020 – Volume 70 – Issue 3 – p 389-403 doi: 10.1097/MPG.0000000000002567
- Crowley E, Muise A. Inflammatory Bowel Disease: What Very Early Onset Disease Teaches Us. Gastroenterol Clin North Am. 2018 Dec;47(4):755-772. doi: 10.1016/j.gtc.2018.07.004. Epub 2018 Oct 4. PMID: 30337031.
- Ouahed, J.,Spencer,E.,Kotlarz, D., Shouval, D. S., Kowalik, M., Peng, K., Field, M., Grushkin-Lerner, L., Pai, S., Bousvaros, A., Cho, J., Argmann, C., Schadt, E., McGovern, D.P.B., Mokry, M., Nieuwenhuis, E., Clevers, H., Powrie, F., Uhlig, H., … Snapper, S. B. (2019). Very early onset inflammatory bowel disease: A clinical approach with a focus on the role of genetics and underlying immune deficiencies. Inflammatory Bowel Diseases, 26(6), 820-842. https://doi.org/10.1093/ibd/izz259
- Uhlig HH, Schwerd T, Koletzko S, et al. COLORS in IBD Study Group and NEOPICS. The diagnostic approach to monogenic very early onset inflammatory bowel disease. Gastroenterology2014; 147:990.e3–1007.e3.
- Muise AM, Snapper SB, Kugathasan S. The age of gene discovery in very early onset inflammatory bowel disease. Gastroenterology2012; 143:285–288.
Consortium/Ongoing Studies: